Cannabidiol enhances the inhibitory effects of Δ9-tetrahydrocannabinol on human glioblastoma cell proliferation and survival

Molecular Cancer Therapeutics

Δ9-THC and other cannabinoids can act as direct anticancer agents in multiple types of cancer in culture and in vivo. 

Individually, Δ9-THC and CBD can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death.

We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes.

We found this to be true in this investigation.

CBD enhances the inhibitory effects of Δ9-THC on glioblastoma cell growth.

Cannabidiol significantly improved the inhibitory effects of Δ9-tetrahydrocannabinol on glioblastoma cell proliferation and survival.

The Combination Treatment of Δ9-THC and Cannabidiol Inhibits Cell Cycle and Induces Apoptosis.

Our results suggest that the addition of CBD to Δ9-THC may improve the overall effectiveness of Δ9-THC in the treatment of glioblastoma in cancer patients.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806496/

http://mct.aacrjournals.org/content/9/1/180.full

“CBD Enhances the Anticancer Effects of THC”  https://www.scribd.com/document/50154001/CBD-Enhances-the-Anticancer-Effects-of-THC-Journal-MCT-Marcu

Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype.

“Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis…

Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors…

In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.”

http://www.ncbi.nlm.nih.gov/pubmed/23892791

Cannabidiol Normalizes Caspase 3, Synaptophysin, and Mitochondrial Fission Protein DNM1L Expression Levels in Rats with Brain Iron Overload: Implications for Neuroprotection.

“We have recently shown that chronic treatment with cannabidiol (CBD) was able to recover memory deficits induced by brain iron loading in a dose-dependent manner in rats.

 Brain iron accumulation is implicated in the pathogenesis of neurodegenerative diseases, including Parkinson’s and Alzheimer’s, and has been related to cognitive deficits in animals and human subjects.

…we have analyzed the expression level of brain proteins involved with mitochondrial fusion and fission mechanisms (DNM1L and OPA1), the main integral transmembrane protein of synaptic vesicles (synaptophysin), and caspase 3, an apoptosis-related protein, to gain a better understanding of the potential of CBD in restoring the damage caused by iron loading in rats.

We found that CBD rescued iron-induced effects…

Our results suggest that iron affects mitochondrial dynamics, possibly trigging synaptic loss and apoptotic cell death and indicate that CBD should be considered as a potential molecule with memory-rescuing and neuroprotective properties to be used in the treatment of cognitive deficits observed in neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23893294

Memory-rescuing effects of cannabidiol in an animal model of cognitive impairment relevant to neurodegenerative disorders.

“Cannabidiol, the main nonpsychotropic constituent of Cannabis sativa, possesses a large number of pharmacological effects including anticonvulsive, sedative, hypnotic, anxiolytic, antipsychotic, anti-inflammatory, and neuroprotective, as demonstrated in clinical and preclinical studies.

 Many neurodegenerative disorders involve cognitive deficits, and this has led to interest in whether cannabidiol could be useful in the treatment of memory impairment associated to these diseases…

We used an animal model of cognitive impairment induced by iron overload in order to test the effects of cannabidiol in memory-impaired rats…

RESULTS:

A single acute injection of cannabidiol at the highest dose was able to recover memory in iron-treated rats. Chronic cannabidiol improved recognition memory in iron-treated rats. Acute or chronic cannabidiol does not affect memory in control rats.

CONCLUSIONS:

The present findings provide evidence suggesting the potential use of cannabidiol for the treatment of cognitive decline associated with neurodegenerative disorders.

 Further studies, including clinical trials, are warranted to determine the usefulness of cannabidiol in humans suffering from neurodegenerative disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21870037

Marijuana Compound Shows Promise In Fighting Breast Cancer

“A compound found in cannabis may prove to be effective at helping stop the spread of breast cancer cells throughout the body.”

 

 
“The study, by scientists at the California Pacific Medical Center Research Institute, is raising hope that CBD, a compound found in Cannabis sativa, could be the first non-toxic agent to show promise in treating metastatic forms of breast cancer.”
 
 

“Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells”  http://mct.aacrjournals.org/content/6/11/2921.full

Cannabis based spray approved for MS

“Sativex licensed for spasticity in multiple sclerosis. MS charity calls it a ‘milestone’
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sad woman
 
“The cannabis-based mouth spray, Sativex, has been approved by the UK medicines regulator, MHRA, as a prescription only treatment for MS related spasticity.

Sativex is designed as an add-on treatment for moderate to severe MS spasms and cramping in people who receive inadequate relief from the standard oral anti-spasticity medicines or have experienced unbearable side effects whilst taking these medicines.

Sativex contains two cannabinoids or active ingredients – THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol).  It is the first cannabinoid medicine derived from whole plant extracts from the cannabis sativa plant…”

More: http://www.webmd.boots.com/news/20100621/cannabis-based-spray-approved-for-ms

Aylsham multiple sclerosis sufferer says cannabis-based drug ‘changed my life’

“A new cannabis-based licensed drug has transformed the life of multiple sclerosis (MS) sufferer Teresa Pointer from Aylsham.”

Teresa Pointer, from Aylsham, whose MS has been helped by using a new drug based on cannabis plant extracts.
PHOTO: ANTONY KELLY

“Mrs Pointer, 42, spotted an advertisement in the EDP eight years ago, asking people to take part in treatment trials at the James Paget University Hospital, Gorleston, and she has not looked back.

Today, thanks to two daily sprays of Sativex into her mouth, Mrs Pointer can sleep at night, walk for longer – and she has got her sense of humour back.

“I got in touch with Dr Willy Notcutt at the James Paget and then started on a clinical trial of Sativex. It was the best decision I’ve ever made and it’s done so much for me. It really has given me my life back,” said Mrs Pointer, who lives with her husband and two daughters in Hungate Street.

She was diagnosed in 2004 with MS, a disease which affects nerves in the brain and spinal cord.

An increase in muscle tone, or “spasticity”, is a common symptom, causing involuntary muscle spasms, immobility, disturbed sleep, and pain.

Although MS is incurable, treatments and specialists can help sufferers manage their symptoms.

Within two weeks of starting the trial, Mrs Pointer, whose health problems forced her to retire from her job as an assistant cook at Aylsham’s Bure Valley School, began to notice an improvement.

“It doesn’t take any of the symptoms away but it relieves them,” she said. The drug relaxed her muscles, easing the pain, discomfort and spasms when her legs would “try and jump off the bed”, which stopped her sleeping.

“I had been getting so tetchy through lack of sleep. I was snappy and angry all the time. But, because it helped me sleep, I could laugh and smile again. I found the funnier side of life which I thought I’d lost forever.”

At a later point in the double-blind trial, which involved 18 local patients, Mrs Pointer, without her knowledge or that of the medical team, was given a placebo instead of Sativex. Her symptoms soon returned and she could not sleep.

After discussions with specialists, she was put back on the drug. “That night I slept like a baby again. The contrast was so stark,” she said.

Mrs Pointer said she had no previous experience of cannabis but Sativex only relaxed muscles, it did not generate the “high” sought by recreational drug users.

She also believes that, without the drug, she would be using her wheelchair far more often than she does at present as it relaxes her leg muscles enough to allow her to walk greater distances.

Dr Notcutt, research and development director at the James Paget, said Mrs Pointer’s participation in the trial had been invaluable.

He added: “The results of these studies are being used all across the world as doctors and others look at the potential value of this medicine. Teresa and others like her locally have been pioneers in a therapy that has a huge potential in many different areas. Without more volunteers to help us explore, medical research will only make very slow progress.”

■ Around 100,000 people in the UK have MS. It is normally diagnosed in people between the ages of 20 and 40, and affects almost three times as many women as men.

■ Sativex, in the form of a mouth spray, contains the principal extracts delta-9-tetrahydrocannabinol and cannabidiol – found in the leaf and flower of the cannabis plant, and is the first cannabinoid preparation to be licensed in the UK for use in the treatment of muscle spasms in MS.”

http://www.eveningnews24.co.uk/mobile/news/aylsham_multiple_sclerosis_sufferer_says_cannabis_based_drug_changed_my_life_1_2276182

[Marihuana and cannobinoids as medicaments].

“Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen.

Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting.

Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease.

Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells.

Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications.

In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin.

Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.”

http://www.ncbi.nlm.nih.gov/pubmed/23421098

Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.

“Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors.

Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation.

Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation.

OBJECTIVE:

We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors.

CONCLUSION:

The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process.

 Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.”

http://www.ncbi.nlm.nih.gov/pubmed/17157480

Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.

“A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.

CONCLUSIONS AND IMPLICATIONS:

These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23869687